Hyaluronan modulates cell proliferation and mRNA expression of adhesion-related procollagens and cytokines in glenohumeral synovial/capsular fibroblasts in adhesive capsulitis.

There is a growing body of evidence supporting the use of hyaluronan (HA) in patients with adhesive capsulitis of the shoulder, although the mechanisms of the effect have not yet been clarified. This in vitro study examined the effects of HA on glenohumeral synovial/capsular fibroblasts (GSCFs) from patients with adhesive capsulitis of the shoulder. The study subjects were seven patients with primary or secondary adhesive capsulitis of the shoulder (average age: 55 years; range: 42-65). Synovial/capsular specimens were obtained from the rotator interval of each patient during arthroscopy. Part of the tissue specimen was used for histological analysis. The remainder of the tissue was prepared for cell culture. Various concentrations of HA (0.0-4.0 mg/mL) were added to the monolayer-cultured GSCFs from these patients. Histological analysis consistently demonstrated chronic nonspecific inflammation with synovial hyperplasia, proliferation of vessels and fibroblasts, and increased amount of extracellular matrix. Treatment with HA at various concentrations significantly and dose-dependently inhibited cell proliferation and decreased the expression levels of mRNA for adhesion-related procollagens and cytokines. Pretreatment with OS/37 did not reverse the inhibitory effect of HA. These results suggest that HA modulates cell proliferation and expression of the mRNA of adhesion-related procollagens and cytokines in GSCFs, preventing the progression of adhesion formation in patients with adhesive capsulitis of the shoulder.

Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase-2/prostaglandin E(2) production via CD44 in interleukin-1-stimulated subacromial synovial fibroblasts from patients with rotator cuff disease.

A growing body of evidence supports use of intraarticular hyaluronic acid (HA) injection in patients with rotator cuff disease. However, the mechanism of its anti-inflammatory action has not been clarified. We examined the effects of HA on the expression of mRNAs for proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha and COX-2/PGE(2) production in IL-1-stimulated subacromial-synovium fibroblasts (SSF) derived from patients with rotator cuff disease. Various concentrations of HA were added to monolayer SSF cultures in the presence of IL-1beta. Gene expression levels were analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Intracellular production of COX-2 was identified by Western blotting. PGE(2) concentrations in the culture media were measured by ELISA. CD44 blocking with OS/37 was performed to investigate the mechanism of action of HA. Immunofluorescence cytochemistry confirmed binding of HA and the presence of CD44 on SSF. Exogenous HA significantly and dose-dependently decreased expression of proinflammatory cytokine mRNAs and COX-2/PGE(2) production in IL-1-stimulated SSF. Pretreatment with OS/37 reversed the inhibitory effects of HA. These results provide a basis for explaining why HA is effective for the treatment of rotator cuff disease.